Benzodiazepine (Bz) receptors are recently classified into 2 subtypes of central benzodiazepine receptor (CBR) located on GABA.sub.A receptor/ion channel complex and mitochondrial DBI (diazepam binding inhibitor, Neuropharmacol., 30, 1425-1433 (1991)) receptor (BDR) located on the central nervous system (glial cells) or adrenal glands (Clin. Neuropharmacol., 16, 401-417 (1993)).
MDR agonists act indirectly on GABA.sub.A /ion channel complex via endogenous neurosteroids and cause an anti-anxiety action. Accordingly, they have a possibility to be usable for diseases (obsessive disorders, panic disorders) on which the previous Bzs do not have a satisfactorily therapeutic effect, and to alleviate side-effects such as excessive sedation or psychic dependence caused by the Bzs. Furthermore, MDR ligands act indirectly on GABA.sub.A receptors, and therefore, have a possibility of use as therapeutical agents of sleeping disorders, epilepsy, dyskinesia accompanied by muscle rigidity, feeding disorders, circulation disorders, recognition and learning disability or drug dependence (Progress in Neurobiology, 38, 379-395, 1992, ibid., 49, 73-97, 1996; J. Neurochem., 58, 1589-1601; Neuropharmacol., 30, 1435-1440, 1991). In addition, MDR ligands have a possibility of use as therapeutic agents of cancer (Biochimica et Biophysica Acta, 1241, 453-470, 1995), lipid metabolism abnormality (Eur. J. Pharmacol., 294, 601-607, 1995), schizophrenia (Neuropharmacology, 35, 1075-1079, 1996), cerebral infarction (J. Neurosci., 15, 5263-5274, 1995), AIDS (Abstracts of the fifth international conference on AIDS, p. 458, 1989), Alzheimer's disease (Alzheimer Dis. Assoc. Disotd., 2, 331-336, 1988) or Huntington chorea (Brain Res., 248, 396-401, 1982).
Some phenoxyaniline derivatives are reported in WO9533715, JP 61040249 and JP 57208295. However, they have a hydrogen atom or an alkyl group as the substituent on the nitrogen atom of the aniline, but there are not reported the derivatives having a carbonyl group as the substituent. Furthermore, the use of the derivatives of the above-mentioned patent is anti-inflammatory agents based on the action to arakidonic acid series, anti-arteriosclerosis drugs based on an increase of PGI.sub.2 production, or heat sensitive recording materials, but there is not described affinity for MDR and anti-anxiety based on affinity for MDR.
An object of the present invention is to provide pharmaceutical compounds which are effective on diseases on which the previous Bzs do not have a satisfactorily therapeutic effect, and have a high affinity for MDR, and therefore, have a therapeutic or preventive effect on the central diseases such as anxiety, related diseases thereto, depression, epilepsy, etc. without side-effects such as excessive sedation or psychic dependence caused by the Bzs. Furthermore, another object of the present invention is to provide therapeutic agents of sleeping disorders, dyskinesia accompanied by muscle rigidity, feeding disorders, circulation disorders, recognition and learning disability, drug dependence, cancer, lipid metabolism abnormality, schizophrenia, cerebral infarction, AIDS, Alzheimer's disease or Huntington chorea.